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Comparación de surfactantes de origen animal para la prevención y el tratamiento del síndrome de dificultad respiratoria en lactantes prematuros

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Referencias

References to studies included in this review

Attar 2004 {published data only}

Attar MA, Becker MA, Dechert RE. Immediate change in lung compliance following natural surfactant administration in premature infants with respiratory distress syndrome. Journal of Perinatology 2004;24(10):626‐30.

Baroutis 2003 {published data only}

Baroutis G, Kaleyias J, Liarou T. Comparison of three treatment regimens of the natural surfactant preparations in neonatal respiratory distress syndrome. European Journal of Pediatrics 2003;162(7‐8):476‐80.

Bloom 1997 {published data only}

Bloom BT,  Kattwinkel J,  Hall RT,  Delmore PM,  Egan EA,  Trout JR,  et al. Comparison of Infasurf (calf lung surfactant extract) to Survanta (Beractant) in the treatment and prevention of respiratory distress syndrome. Pediatrics 1997;100(1):31‐8.

Bloom 2005 {published data only}

Bloom BT, Clark RH for Infasurf Survanta Clinical Trial group. Comparision of Infasurf (calfactant) and Survanta (beractant) in the prevention of respiratory distress syndrome. Pediatrics 2005;116(2):392‐9.

Didzar 2012 {published data only}

Dizdar EA,  Sari FN,  Aydemir C,  Oguz SS,  Erdeve O,  Uras N,  et al. A randomized, controlled trial of poractant alfa versus beractant in the treatment of preterm infants with respiratory distress syndrome. American Journal of Perinatology 2012;29(2):95‐100.

Fujii 2010 {published data only}

Fujii AM, Patel SM, Allen R. Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome. Journal of Perinatology 2010;30(10):665‐70.

Gharehbaghi 2010 {published data only}

Gharehbaghi MM,  Sakha SH,  Ghojazadeh M,  Firoozi F. Complications among premature neonates treated with beractant and poractant alfa. Indian Journal of Pediatrics 2010;77(7):751‐4.

Halahakoon 1999 {published data only}

Halahakoon WL. A study of cerebral function following surfactant treatment for respiratory distress syndrome (Doctoral dissertation). Queen's University of Belfast (UK)1999.

Hammoud 2004 {published data only}

Hammoud M,  Al‐Kazmi N,  Alshemmiri M,  Thalib L,  Ranjani VT,  Devarajan LV,  et al. Randomized clinical trial comparing two natural surfactant preparations to treat respiratory distress syndrome. Journal of Maternal Fetal and Neonatal Medicine 2004;15(3):167‐75.

Karadag 2014 {published data only}

Karadag N, Dilli D, Zenciroglu A, Aydin B, Beken S, Okumus N. Perfusion index variability in preterm infants treated with two different natural surfactants for respiratory distress syndrome. American Journal of Perinatology 2014;31(11):1015‐22. [PUBMED: 24566756]

Lam 2005 {published data only}

Lam BC,  Ng YK,  Wong KY. Randomized trial comparing two natural surfactants (Survanta vs bLES) for treatment of neonatal respiratory distress syndrome. Pediatric Pulmonology 2005;39(1):64‐9.

Malloy 2005 {published data only}

Malloy CA, Nicoski P, Muraskas JK. A randomized trial comparing beractant and poractant treatment in neonatal respiratory distress syndrome. Acta Paediatrica 2005;94(6):779‐84.

Ramanathan 2004 {published data only}

Ramanathan R,  Rasmussen MR,  Gerstmann DR,  Finer N,  Sekar K,  North American Study Group. A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. American Journal of Perinatology 2004;21(3):109‐19.

Sanchez‐Mendiola 2005 {published data only}

Sánchez‐Mendiola M,  Martínez‐Natera OC,  Herrera‐Maldonado N,  Ortega‐Arroyo J. Treatment of hyaline membrane disease in the preterm newborn with exogenous lung surfactant: a controlled study [Estudio controlado del tratamiento de la enfermedad de membrana hialina del recien nacido pretermino con surfactante pulmonar exogeno (porcino vs bovino)]. Gaceta medica Mexico 2005;141(4):267‐71.

Speer 1995 {published data only}

Speer CP, Gefeller O, Groneck P. Randomized clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome. Archives of Disease in Childhood 1995;72(1):F8‐13.

Yalaz 2004 {published data only}

Yalaz M, Aslanoglu S, Akisu M, Atik T,  Ergun O,  Kultursay N. A comparison of efficacy between two natural exogenous surfactant preparations in premature infants with respiratory distress syndrome. Klinische Padiatrie 2004;216(4):230‐5.

References to studies excluded from this review

Bozdağ 2015 {published data only}

Bozdağ S, Dilli D, Gökmen T, Dilmen U. Comparison of two natural surfactants for pulmonary hemorrhage in very low‐birth‐weight infants: a randomized controlled trial. American Journal of Perinatology 2015;32(3):211‐8.

Choi 2005 {published data only}

Choi CW,  Hwang JH,  Yoo EJ,  Kim KA,  Koh SY,  Lee YK,  et al. Comparison of clinical efficacy of Newfactan versus Surfacten for the treatment of respiratory distress syndrome in he newborn infants. Journal of Korean Medical Science 2005;20(4):591‐7.

Proquitté 2007 {published data only}

Proquitté H, Dushe T, Hammer H, Rüdiger M, Schmalisch, G, Wauer RR, et al. Observational study to compare the clinical efficacy of the natural surfactants Alveofact and Curosurf in the treatment of respiratory distress syndrome in premature infants. Respiratory Medicine 2007;101(1):169‐76.

Rebello 2009 {unpublished data only}

Rebello CM, Mascaretti RS, Precioso AR. A multicenter randomized double blind trial of a new low cost animal surfactant in premature infants with respiratory distress syndrome. E‐PAS. 2009.
Rebello CM, Precioso AR, Mascaretti RS, Grupo Colaborativo do Estudo Brasileiro Multicêntrico de Surfactante. A multicenter, randomized, double‐blind trial of a new porcine surfactant in premature infants with respiratory distress syndrome. Einstein (Sao Paulo) 2014;12(4):397‐404. [DOI: 10.1590/S1679‐45082014AO3095]

References to studies awaiting assessment

Eras 2014 {published data only}

Eras Z, Dizdar EA, Kanmaz G, Guzoglu N, Aksoy HT, Altunkaya GB, et al. Neurodevelopmental outcomes of very low birth weight preterm infants treated with poractant alfa versus beractant for respiratory distress syndrome. American Journal of Perinatology 2014;31(6):463‐8. [DOI: 10.1055/s‐0033‐1351659]

Gharehbaghi 2014 {published data only}

Gharehbaghi MM, Yasrebi S. Comparing the efficacy of two natural surfactants, Curosurf and Alveofact, in treatment of respiratory distress syndrome in preterm infants. International Journal of Women’s Health and Reproduction Sciences 2014;2(4):245‐8.

Mercado 2010 {published data only}

Mercado VV,  Cristea I,  Ali N,  Pham CC,  Buescher E,  Yang J,  et al. Does surfactant type cause a differential proinflammatory response in preterm infant with respiratory distress syndrome?. Advances in Therapy 2010;27(7):476‐82.

Saeidi 2013 {published data only}

Saeidi R, Hamedi A, Javadi A, Robatsangi MG, Dinparvar SK. Comparison of side effects of survanta and curosurf in decreasing mortality due to respiratory distress syndrome (RDS) in premature infants admitted in NICU of Ghaem Hospital on 2006‐2008. Iranian Journal of Neonatology 2013;4(3):7‐12. [AN:2013708341]

Terek 2015 {published data only}

Terek D, Gonulal D, Koroglu OA, Yalaz M, Akisu M, Kultursay N. Effects of two different exogenous surfactant preparations on serial peripheral perfusion index and tissue carbon monoxide measurements in preterm infants with severe respiratory distress syndrome. Pediatric Neurology 2015;56(4):248‐55.

Avery 1959

Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. American Journal of Diseases in Children 1959;97(5 Pt 1):517‐23.

Bell 1978

Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of Surgery 1978;187(1):1‐7.

Chu 1967

Chu J, Clements JA, Cotton EK, Klaus MH, Sweet AY, Tooley WH. Neonatal pulmonary ischemia. I. Clinical and physiological studies. Pediatrics 1967;40(4):709‐82.

Dargaville 2011

Dargaville PA, Aiyappan A, Cornelius A, Williams C, Antonio G De Paoli. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Archive of Disease in Childhood ‐ Fetal and Neonatal Edition 2011;96(4):F243–8.

Engle 2008

Engle WA, American Academy of Pediatrics Committee on Fetus and Newborn. Surfactant‐replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121(2):419‐32.

Enhorning 1972

Enhorning G, Robertson B. Lung expansion in the premature rabbit fetus after tracheal deposition of surfactant. Pediatrics 1972;50(1):58‐66.

Fujiwara 1980

Fujiwara T, Maeta H, Chida S, Morita T, Watabe YJ, Abe T. Artificial surfactant therapy in hyaline membrane disease. Lancet 1980;I(8159):55‐9.

GradePro 2008 [Computer program]

Jan Brozek, Andrew Oxman, Holger Schünemann. GradePro [Version 3.2 for Windows]. 2008.

Guyatt 2011a

Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. Journal of clinical epidemiology 2011;64(4):383‐94. [PUBMED: 21195583]

Guyatt 2011b

Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso‐Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence‐‐study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407‐15. [PUBMED: 21247734]

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Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso‐Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence‐‐imprecision. Journal of clinical epidemiology 2011;64(12):1283‐93. [PUBMED: 21839614]

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Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence‐‐inconsistency. Journal of clinical epidemiology 2011;64(12):1294‐302. [PUBMED: 21803546]

Guyatt 2011e

Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence‐‐indirectness. Journal of clinical epidemiology 2011;64(12):1303‐10. [PUBMED: 21802903]

Halliday 2008

Halliday HL. Surfactants: past, present and future. Journal of Perinatology 2008;28(Suppl 1):S47‐S56.

Hawgood 1985

Hawgood S, Benson BJ, Hamilton Jr RL. Effects of surfactant‐associated proteins and calcium ions on the structure and surface activity of lung surfactant lipids. Biochemistry 1985;24(1):184‐90.

Higgins 2011

Higgins A, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

ICCROP 2005

International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Archives of Ophthalmology 2005;123(7):991‐9.

Jobe 1993

Jobe AH. Pulmonary surfactant therapy. New England Journal of Medicine 1993;328(1):861‐8.

Kribs 2007

Kribs A, Pillekamp F, Hunseler C. Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age < 27 weeks). Pediatric Anesthesia 2007;17(4):364‐9.

Moya 2009

Logan JW, Moya FR. Animal derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials. Therapeutic and Clinical Risk Management 2009;5(1):251‐60.

Papile 1978

Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92(4):529‐34.

Pfister 2007

Pfister RH, Soll RF, Wiswell T. Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006069.pub3]

Pfister 2009

Pfister RH, Soll R, Wiswell TE. Protein‐containing synthetic surfactant versus protein‐free synthetic surfactant for the prevention and treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD006180.pub2]

Ramanathan 2009

Ramanathan R. Animal derived surfactants: where are we? The evidence from randomized controlled trials. Journal of Perinatology 2009;29(Suppl 2):s38‐43.

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Robillard E, Alarie Y, Dagenais‐Perusse P, Baril E, Guilbeault A. Microaerosol administration of synthetic beta‐gamma‐dipalmitoyl‐L‐alpha‐lecithin in the respiratory distress syndrome. Canadian Medical Association Journal 1964;90:55‐7.

Rojas‐Reyes 2012

Rojas‐Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD000510.pub2]

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Singh N, Hawley KL, Viswanathan K. Efficacy of porcine versus bovine surfactants for preterm newborns with respiratory distress syndrome: systematic review and meta‐analysis. Pediatrics 2011;128(6):e1588‐95.

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Soll RF, McQueen MC. Respiratory Distress Syndrome. Sinclair J, Bracken M: Effective Care of the Newborn Infant. New York: Oxford University Press, 1992:325‐58. [ISBN 0‐19‐261737‐0]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Attar 2004

Methods

Randomized Single Center

Participants

Total participants = 40

Preterm infants < 37 weeks' gestation

Chest radiograph consistent with RDS

Required intubation and mechanical ventilation

Need for surfactant determined by the care providing team

Randomized 40 infants to receive calfactant (n = 19, BW (g) 1621 ± 442 and GA (wk) 30.0 ± 2.1)) and beractant (n = 21, BW (g) 1309 ± 642 and GA (wk) 29.0 ± 3.6)).

Interventions

Calfactant (n = 19)

Dose: 100 mg/kg phospholipid

Beractant (n = 21)

Dose = 100 mg/kg phospholipid

Repeat dose given as per manufacturer’s instruction

Criteria for re‐dosing: Objective

Same technique for surfactant administration

Outcomes

Primary: Dynamic compliance 1 hour following first dose of surfactant administration

Secondary outcomes: chronic lung disease (need for oxygen at 36 weeks' PMA); Early onset sepsis

PDA; survival (alive at hospital discharge)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomly assigned to treatment options by sampling replacement. Unclear sequence generation.

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Unmasked

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Unmasked

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No infants lost to follow‐up

Selective reporting (reporting bias)

Low risk

Reported on primary outcome (dynamic compliance 1 hour after first dose of surfactant) as well as important secondary outcomes (chronic lung disease (need for oxygen at 36 weeks' PMA); early onset sepsis; PDA; survival (alive at hospital discharge).

Other bias

Low risk

Baroutis 2003

Methods

Randomized Single Center

Participants

Total participants = 82

Preterm infants ≤ 32 weeks' gestational age and ≤ 2000 g

RDS requiring mechanical ventilation and FiO₂ requirement ≥ 0.30

The groups were comparable for GA and BW (29.0 ± 1.2 wk and 1195 ± 390 g in bovactant (Alveofact) group; 28.7 ± 0.5 wk and 1233 ± 380 g in poractant alfa group; and 29.2 ± 1.0 wk and 1180 ± 410 g in beractant group).

Interventions

Bovactant (Alveofact) (n = 27)

Dose 100 mg/kg

Poractant alfa (n = 27)

Dose: 100 mg/kg

Beractant (n = 28)

Dose: 100 mg/kg

Repeat dose after 12 h

Outcomes

Chronic lung disease (oxygen requirement at 36 weeks' PMA); PDA; pulmonary air leak; ROP; IVH

Notes

Bovactant (Alveofact) and poractant alfa given as rapid bolus

Beractant was given slowly by pump via adaptor (not as bolus as recommended by manufacturer)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomization not described

Allocation concealment (selection bias)

Low risk

Sealed envelope

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Different method of administration of surfactant, hence blinding of personnel not possible

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Standardized ventilator protocol for initiation and weaning of ventilator, but description of an attempt to blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Bloom 1997

Methods

Randomized Multicenter Double Blinded

Participants

Treatment arm: Total participants: 483

Preterm infants with birth weight < 2000 g with established RDS and < 48 h of age

Requiring intubation and mechanical ventilation

FiO₂ ≥ 0.40

Prevention arm: Total participants = 499

Preterm infants ≤ 29 weeks' gestation and birth weight ≤ 1250 g

Infants in the treatment arm were more mature and heavier compared with the prevention arm.

In treatment arm, the mean (SD) gestational age and birth weight were 29.2 ± 2.8 wk & 1162 ± 408 g in calfactant group and 29.2 ± 2.8 wk & 1166 ± 401 g in beractant group.

In prevention arm, mean (SD) gestational age and birth weight were 27.1 ± 2.2 wk & 891 ± 221 g in calfactant group and 27.1 ± 2.1 wk and 845 ± 205 g in beractant group.

Interventions

Calfactant

Dose: 100 mg/kg

Beractant

Dose: 100 mg/kg

Repeat dosing: 3 repeat treatments given if infant remained intubated for RDS and FiO₂ ≥ 0.30 within first 96 h of life

Outcomes

Primary outcome

Decrease in need for third dose of surfactant with established RDS

Decrease in need for second repeat dose with prophylactic surfactant administration

Notes

Special 25 mg/ml concentration of calfactant used in the trial to maintain masking. Administration, storage and dispensing of surfactant followed beractant package insert

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random assignment

Variable block size randomizations by pseudo‐random number generation

Allocation concealment (selection bias)

Low risk

Allocation of patient by selection of the next vial from box of sequentially numbered vials

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Surfactants were provided in a vial covered by two layers of opaque labels. The surfactant products were similar in consistency, concentration and color

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

A data co‐ordinator and a neonatologist designated to collect data

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Bloom 2005

Methods

Randomized Multicenter

Participants

Total participants:

Treatment arm (n = 1361)

Preterm infants with birth weight 401 to 2000 g and < 36 h of age

FiO₂ requirement ≥ 0.40
No previous surfactant therapy

Prevention arm (n = 749)

Preterm infants 23 to 29 + 6/7 weeks' gestation, randomized at birth

Infants in the treatment arm were older and larger compared with the prevention arm.

In treatment arm, the mean (SD) for GA (wk) and BW (g) were 28.4 ± 2.8 & 1154 ± 402 in beractant group and 28.4 ± 2.7 & 1155 ± 408 in calfactant group.

In prevention arm, the mean (SD) GA (wk) and BW (g) were 26.6 ± 1.9 & 907 ± 275 in beractant group and 26.5 ± 2 & 910 ± 287 in calfactant group.

Interventions

Calfactant

Dose: 105 mg/kg

Beractant

Dose: 100 mg/kg

Repeat dosing: maximum of 3 repeat doses 6 h apart if infant remained intubated for RDS and had FiO₂ requirement ≥ 0.30 to keep SpO₂ > 90%

Outcomes

Primary outcome: Percent infants alive at 36 weeks' PMA without use of supplemental oxygen requirement

Secondary outcome: Death from respiratory failure; air leak; severe brain injury (IVH grade 3 or 4 or PVL)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Balanced randomization schedule

Computerized random number generation

Twins and multiples randomized as individuals

Allocation concealment (selection bias)

Low risk

Sealed envelopes used

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Masked syringes used to administer surfactant by personnel not involved in direct patient care

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Reported to maintain blind during statistical analysis

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Unclear risk

Terminated early due to poor enrollment

Didzar 2012

Methods

Randomized Single Center

Participants

Total participants = 126

Preterm infants < 37 weeks' gestation

Clinical and radiological diagnosis of RDS within 6 h of birth

FiO₂ ≥ 0.30 to maintain SpO₂ 88% to 96%

The median gestational age and birth weight was 28 wk and 1165 g in poractant group; and 28 wk and 1080 g in beractant group. The rate of antenatal steroid coverage was 63% for poractant group and 51% for beractant group

Interventions

Poractant alfa (n = 61)

Dose: 200 mg/kg

Beractant (n = 65)

Dose: 100 mg/kg

Repeat dose given if FiO₂ ≥ 0.30 at 100 mg/kg for both poractant alfa and beractant

Outcomes

Primary outcome: FiO₂ requirement after 24 h following surfactant administration

Secondary outcomes: Need for repeat dose; duration for respiratory support; duration of hospitalization; and other key morbidities related to prematurity

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomization process not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Reported on key morbidities related to prematurity

Other bias

Low risk

Fujii 2010

Methods

Randomized Single Center

"open label" trial

Participants

Total participants = 52

Preterm infants between 24 + 0/7 to 29 + 6/7 weeks’ GA

Inborn

RDS requiring mechanical ventilation

Randomized within 6 h

The mean (SD) gestational age and birth weight was 27.1 (1.6) wk and 930 (231) g in poractant group; and 26.7(1.7) wk and 900 (271) g in beractant group.

Interventions

Portactant alfa (n = 25)

Dose: 200 mg/kg

Beractant (n = 27)

Dose: 100 mg/kg

Repeat dose at 100 mg/kg for both groups if FiO₂ requirement remains ≥ 0.30

Outcomes

Primary outcome: Short‐term outcome of prematurity

FiO₂ requirement, MAP and MAP X FiO₂ until 72 h

Secondary outcomes: Key morbidities related to prematurity.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization using SAS software with variable block size design

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding for either the participants or personnel was reported.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

None

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up.

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Gharehbaghi 2010

Methods

Quasi‐randomized Single Center

Participants

Total participants = 150

Newborns diagnosed with RDS requiring exogenous surfactant

The mean (SD) gestational age and birth weight was 29.4 (2.4) wk and 1435 (642) g in poractant group; and 29.5 (2.7) wk and 1450 (519) g in beractant group.

The groups were similar in characteristics. The rate of antenatal steroid exposure was only 45.5% for poractant group and 42.3% for beractant group.

Interventions

Poractant alfa (n = 79)

Dose: 200 mg/kg

Beractant (n = 71)

Dose: 100 mg/kg

Repeat dosing if FiO₂ requirement ≥ 0.50 and radiographic evidence of RDS in presence of continued respiratory distress

Outcomes

Ventilation support requirement at 7 days of age

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Odd or even number of admission code

Allocation concealment (selection bias)

High risk

Odd or even number of admission code

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome reported by two senior neonatologists who did not know the group assignment

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Halahakoon 1999

Methods

As part of her PhD thesis, Halahakoon evaluated the effects of poractant alfa, beractant and colfosceril palmitate (Exosurf Neonatal)

Participants

infants 24 to 32 weeks' gestation with RDS requiring assisted ventilation and FiO₂ > 0.40 at < 12 h of age

poractant alfa at 100 mg/kg (n = 17, mean (SD) birth weight of 926 (278) g, mean (SD) gestational age of 26.8 (2.4) wk),

colfosceril palmitate at 67.5 mg/kg (n = 12, mean (SD) birth weight of 956 (233) g, mean (SD) gestational age of 26.9 (1.9) wk) and beractant at 100 mg/kg (n = 10, mean (SD) birth weight of 1011 (327) g, mean (SD) gestational age of 27.3 (2.0) wk).

Interventions

poractant alfa (n = 17), beractant (n = 10) and colfosceril palmitate (Exosurf neonatal) (n = 12)

Outcomes

cerebral function, hypoxanthine levels and antioxidant levels

Notes

Clinical data are being sought for possible inclusion

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Not described

Allocation concealment (selection bias)

Low risk

Sealed envelopes opened at the time of randomization

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

No

Other bias

Low risk

Hammoud 2004

Methods

Randomized Single Center

Participants

Total participants = 109

Preterm infants < 34 weeks' gestation

Requiring intubation and mechanical ventilation for RDS within 6 h of birth

FiO₂ ≥ 0.40 to maintain SpO₂ > 90%

The mean (SD) GA and BW were 28.5 ± 4.4 wk & 1031 ± 298 g in the bovactant (Alveofact) group and 29.2 ± 2.3 wk & 1078 ± 279 g in beractant group

Interventions

Bovactant (n = 54)

Dose: 50 mg/kg phospholipid

Beractant (n = 55)

Dose: 100 mg/kg phospholipid

Repeat dosing (up to 3 doses) given if patient still requiring mechanical ventilation and FiO₂ ≥ 0.30 until 48 h of age

Outcomes

Primary outcome: Chronic lung disease (oxygen requirement at 28 days)

Secondary outcomes: Severity of RDS as assessed by FiO₂; oxygenation index, a/A PO₂; MAP; Pneumothorax; IVH; PDA; days on mechanical ventilation; days of hospitalization

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Assessment team drawn from the NICU who were not involved in surfactant administration

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Other bias

Low risk

Karadag 2014

Methods

The objective of this study was to compare the perfusion index (PI) variability in premature infants with respiratory distress syndrome (RDS) following administration of two different animal‐derived surfactant preparations.

Participants

Prospective study on 92 preterm infants with RDS.

The mean (SD) birth weight and gestational age was 1098 (256) g and 29.6 (1.8) wk in poractant alfa group; and 1086 (248) g and 29 (1.9) wk in beractant group. The rate of antenatal steroid coverage was 76% in poractant alfa group and 82% in beractant group.

Interventions

Patients were randomized into two groups. Group 1 (n = 46) received beractant; Group 2 (n = 46) received poractant alfa.

Outcomes

Surfactant dosing, oxygenation index (OI), perfusion index (PI). Clinical outcomes including pulmonary hemorrhage, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and mortality.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number generation

Allocation concealment (selection bias)

Low risk

Sealed envelops contained cards that were randomly assigned to the groups

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Reported on key morbidities of prematurity

Other bias

Low risk

Lam 2005

Methods

Randomized Single Center

Participants

Total participants = 63

Preterm infants with birth weights 500 to 1800 g

Clinical or radiological diagnosis of RDS

Requiring intubation and mechanical ventilation for RDS

The mean (SD) BW and GA were 1038 ± 263 g and 27.5 ± 1.9 wk in the bLES group and 971 ± 299 g and 26.9 ± 2.3 wk in beractant group.

Interventions

bLES (n = 29)

Dose: 135 mg/kg phospholipid

Beractant (n = 31)

Dose: 100 mg/kg phospholipid

Objective criteria for repeat dosing: FiO₂ > 0.10 compared with FiO₂ requirement after first dose of surfactant

Outcomes

Primary outcome: Oxygenation Index

Secondary outcomes: Chronic lung disease (oxygen requirement at 36 weeks' PMA); duration on ventilator; days on oxygen; mortality before hospital discharge

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization based on computer‐generated codes

Stratified by birth weight

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Malloy 2005

Methods

Randomized Single Center

Participants

Total = 58

Preterm infants < 37 weeks' gestation

Clinical signs and symptoms of RDS requiring intubation and surfactant as per clinical judgement

Surfactant administration routine at ≤ 28 weeks' gestation

The mean (SD) gestational age and birth weight was 29.6 (3.6) wk and 1394 (699) g in poractant alfa group; and 29.3 (2.9) wk and 1408 (534) g in beractant group

Interventions

Poractant alfa (n = 29)

Dose: 200 mg/kg

Beractant (n = 29)

Dose: 100 mg/kg

Redosing if FiO₂ requirement ≥ 0.30 and infant remains on mechanical ventilation

Outcomes

Primary outcome: FiO₂ requirement at 48 h after first surfactant dose

Secondary outcomes: Pneumothorax; PDA; IVH, PVL; BPD (oxygen requirement at 28 days and at 36 weeks' PMA); ROP; death

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Allocation concealment (selection bias)

Low risk

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not stated, but infants received different re‐treatment schedules that would be obvious to staff. Written standard protocols for ventilator management and oxygen weaning provided and mandated to minimize performance bias

Blinding of outcome assessment (detection bias)
All outcomes

High risk

The radiologist and cardiologist reported to be masked

Masking for other outcome assessment not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Selective reporting (reporting bias)

Low risk

Other bias

Low risk

Ramanathan 2004

Methods

Randomized

Multicenter Masked Trial

Participants

Total participants = 293

Preterm infants with BW 750 to 1750 g and GA < 35 wk

Clinical or radiographic evidence of RDS

Intubated and mechanically ventilated

FiO₂ ≥ 0.30 OR a/A ratio of ≤ 0.33

The groups were comparable with mean BW (SD) being 1511 (259), 1148 (265), 1187 (275) g and mean GA (SD) being 28.7 (2.0), 28.8 (2.0), 28.7 (2.0) wk for high‐dose poractant alfa, low‐dose poractant alfa, and beractant respectively.

Interventions

Poractant alfa (n = 96)

Dose 100 mg/kg

Poractant alfa (n = 99)

Dose 200 mg/kg

Beractant (n = 98)

Dose 100 mg/kg

Repeat doses for both surfactants at 100 mg/kg

Outcomes

Primary outcome: Area of FiO₂ under curve during 6‐hour period after first dose of surfactant

Secondary outcome: Change in FiO₂, MAP (measured at baselines, 1, 2, 4 and 6 h after first dose); total number of doses of surfactant needed; median duration of oxygen and mechanical ventilation; complications of prematurity

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Using random number, stratified by birth weight

Allocation concealment (selection bias)

Low risk

Opaque and sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Administration of first dose was masked; repeat doses were "unmasked" and given based on individual product recommendations

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Outcome assessors blinded to type or dose of first dose of surfactant (re: assessment of primary outcome)

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Sanchez‐Mendiola 2005

Methods

Randomized Single Center

Participants

Total participants = 44

Interventions

Surfacen: n = 21

Beractant: n = 23

Outcomes

Oxygenation and ventilation index; days on ventilator; days on supplemental oxygen; complications of prematurity; mortality

Notes

Article in Spanish ‐ data obtained from abstract and tables. Further translation requested to determine risk of bias.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Article in Spanish ‐ data obtained from abstract and tables. Further translation requested to determine risk of bias.

Other bias

Unclear risk

Spanish article with limited data

Speer 1995

Methods

Randomized Multicenter Study

Participants

Total participants = 73

Preterm infants with birth weight 700 to 1000 g

Clinical and radiological findings consistent with RDS

FiO₂ requirement ≥ 0.40

The mean (SD) BW and GA were 1095 ± 225 g and 28.9 ± 2.3 wk in the poractant group and 1082 ± 252 g and 28.8 ± 2.2 wk in the beractant group.

Interventions

Poractant alfa (n = 33)

Dose: 200 mg/kg

Beractant (n = 40)

Dose: 100 mg/kg

Repeat dosing with surfactant if FiO₂ ≥ 0.30 and infant remains on mechanical ventilator

Outcomes

Primary outcome: FiO₂ requirement and ventilatory support in first 48 h after surfactant administration

Secondary outcomes; Complications diagnosed within first 28 days of life: PIE; PDA; IVH; pulmonary hemorrhage; sepsis; BPD and death

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomization not reported

Allocation concealment (selection bias)

Low risk

Opaque and sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

"Because the recommended doses, volumes, dose interval and dose procedures differed between both surfactant preparations, blinding of surfactant administration was not feasible"

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Masking of radiologist to the intervention. Masking for other outcome assessment not reported.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

Yalaz 2004

Methods

Randomized Single Center

Participants

Total participants = 50

Preterm infants < 36 weeks' gestation

Radiographic diagnosis of RDS

The groups were comparable with respect to BW, GA and antenatal steroid exposure.

The mean (SD) BW and GA were 1250 ± 356 g and 30.0 ± 2.6 wk in the calfactant group and 1172 ± 397 g and 29.3 ± 2.9 wk in the beractant group.

Interventions

BovactantAlveofact (n = 25)

Dose: 50 mg /kg phospholipid

Beractant (n = 25)

Dose: 100 mg/kg phospholipid

Dose repeated as per manufacturers’ instructions as required based on blood gases and chest X‐ray

Outcomes

Primary outcome: FiO₂, a/A PO₂ and mean airway pressure before and after treatment

Duration of mechanical ventilation

Secondary outcomes: Bronchopulmonary dysplasia (oxygen requirement at 36 weeks' PMA); pneumothorax; mortality

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described. However, it was unlikely as surfactant was administered "according to the manufacturers recommendations, for dosing and method of administration"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up

Selective reporting (reporting bias)

Low risk

Report on key morbidities related to prematurity

Other bias

Low risk

BW: birth weight

g: grams

GA: gestational age

h: hours

IVH: intraventricular hemorrhage

PDA: patent ductus arteriosus

PMA: postmenstrual age

RDS: respiratory distress syndrome

ROP: retinopathy of prematurity

SD: standard deviation

wk: weeks

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Bozdağ 2015

Bozdağ and colleagues conducted a prospective randomized controlled trial to compare the efficacy of two animal‐derived surfactants for pulmonary hemorrhage in very low birth weight (VLBW) infants.

42 infants were divided into two groups, poractant alfa (n = 21) and beractant (n = 21).

Excluded because patient population was VLBW infants with pulmonary hemorrhage.

Choi 2005

Choi and colleagues conducted a multicenter study of a domestically developed bovine surfactant Newfacen compared with Surfacten, another bovine‐derived surfactant for efficacy. A total of 492 preterm infant with established RDS with birth weight < 1500 g were randomly assigned to receive either Newfacen (n = 224) or Surfacten (n = 268). Short‐term responses to surfactant and acute complications such as total doses of surfactant administered and changes in respiratory parameters were studied.

This study was excluded because both the surfactants studied belong to the same comparison group (bovine lung lavage surfactant).

Proquitté 2007

Proquitté and colleagues performed a retrospective, observational study comparing the effects of bovactant (Alveofact) and poractant alfa (Curosurf) on gas exchange and outcome in premature infants.

During a 5‐year period in one German neonatal intensive care unit (NICU), 187 premature infants were treated with surfactant, with 82 receiving bovactant and 105 receiving poractant alfa. The investigators recorded FiO₂ and gas exchange (PaO₂/FiO₂ ratio, PaCO₂, SaO₂) during the first 72 h after surfactant administration and the incidence of outcome parameters at day 28 (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH grade III or IV), patent ductus arteriosus (PDA), pneumothorax, necrotizing enterocolitis (NEC) and death).

The study was excluded as it is not a randomized controlled trial.

Rebello 2009

Rebello and colleagues compared the effects of butantan (a porcine surfactant obtained by organic extraction) with other commercially available surfactants (either beractant or poractant) in preterm infants with RDS.

A total of 327 preterm infants with BW < 1500 g with RDS were randomly assigned to receive butantan (n = 154) and compared with a control group receiving either beractant or poractant (n = 173). The mean BW (SD) and mean GA (SD) were 990 g (245) and 28 wk (2.1) for butantan group and 996 g (235) and 28.1 wk (2.2) for control group respectively.

This study was excluded because control group received both modified bovine lung lavage surfactant and porcine lung lavage surfactant.

BW: birth weight

RDS: respiratory distress syndrome

SD: standard deviation

Characteristics of studies awaiting assessment [ordered by study ID]

Eras 2014

Methods

Prospective, longitudinal, single‐center cohort study

Participants

infants born at ≤ 1,500 g and/or ≤ 32 wk with RDS

Conducted between 2008 and 2009

Interventions

Poractant alfa (n = 113) or beractant (n = 102)

Outcomes

Neurological and developmental assessments were performed at a corrected age of 18 to 24 months

Notes

Unclear whether the patients reported are related to the study of Didzar 2012

Gharehbaghi 2014

Methods

Randomized clinical trial in Alzahra Hospital, Tabriz, Iran

Participants

Preterm newborn infants with gestation age less than 32 wk with RDS

Interventions

Poractant alfa (Curosurf) (N = 66) and bovactant (Alveofact) (N = 64)

Surfactant was administered using the INSURE method (intubation, surfactant administration, extubation)

Outcomes

Ventilator support through 7 days, mean duration of oxygen supplementation and hospital stay and other complications associated with prematurity

Notes

Mercado 2010

Methods

Randomized Single Center

Participants

Total participants = 40

Preterm infants < 30 wk gestation and birth weight < 1000 g

Interventions

Surfactant A (porcine lung extract) (n = 20)

Dose: 200 mg/kg, repeat dose at 100 mg/kg

Surfactant B (Bovine lung extract)(n = 20)

Dose: 100 mg/kg (initial and repeat dose)

Outcomes

Primary outcome: Airway inflammatory response (Cytokine IL‐6 and IL‐8)

Secondary outcomes: BPD (oxygen requirement at 36 weeks' PMA); FiO₂ and oxygenation index at 7 days of life; days of mechanical ventilation; days of hospitalization

Notes

Saeidi 2013

Methods

Clinical trial performed during a 2‐year period in Ghaem Center's neonatal care unit. Method of allocation unknown.

Participants

104 preterm infants were treated with surfactant; 74 in beractant (Survanta) group and 30 in the poractant (Curosurf) group.

Mean gestational age (beractant (Survanta) 30.58 vs poractant (Curosurf) 29.00 wk)

Mean birth weight (beractant (Survanta) 1388 vs poractant (Curosurf) 1330 g)

Interventions

Beractant (Survanta) vs poractant (Curosurf)

Outcomes

bronchopulmonary dysplasia at 28 days, Intraventricular hemorrhage grades III/IV, pneumothorax, patent ductus arteriosis, and death.

Notes

Terek 2015

Methods

Randomized controlled non‐blinded study

Participants

30 preterm infants with RDS, treated with poractant alfa (n = 15) or beractant (n = 15); 18 preterm infants without RDS served as a control group.

Interventions

poractant alfa (n = 15) or beractant (n = 15)

Outcomes

Oxygenation and hemodynamic parameters were recorded and compared through the first 6 h of treatment. Perfusion index (PI) and tissue carbon monoxide (TCO) values were measured prior to (Tp), immediately after (T0), and at 5 minutes (T5), 30 minutes (T30), 60 minutes (T60), and 360 minutes (T360) after the bolus surfactant administration. The mean arterial pressure, oxygenation index, pH, and lactate levels were recorded simultaneously.

Notes

Both study groups had lower Tp PI and higher Tp TCO levels than controls. Both surfactant preparations improved the PI, TCO, mean arterial pressure, oxygenation index, pH, and lactate levels at the end point of T360. However, the median Tp PI value of 1.3 first decreased to 0.86 at T0 (P < 0.001), and then it increased to 0.99 at T5 (p < 0.001) and to 1.25 at T30 (p = 0.037). The median Tp TCO value of 3 decreased to 2, 1.5, 0, and 0 at T0, T5, T30, and T60, respectively (p < 0.001). PI more quickly recovered to Tp values (30 minutes vs. 60 minutes) and reached the control group values (30 minutes vs. 360 minutes) with beractant compared with that with poractant alfa. TCO recovered to Tp values in both groups at the same time (5 minutes vs. 5 minutes), but reached the control group values more quickly (5 minutes vs. 30 minutes) with poractant alfa than with beractant.

BPD: bronchopulmonary dysplasia

g: grams

PMA: postmenstrual age

wk: weeks

Data and analyses

Open in table viewer
Comparison 1. Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 1 Neonatal mortality.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 1 Neonatal mortality.

1.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.79, 1.80]

1.2 Treatment

3

1451

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.65, 1.26]

2 Mortality prior to discharge Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 2 Mortality prior to discharge.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 2 Mortality prior to discharge.

2.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.90, 1.71]

2.2 Treatment

6

2231

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.79, 1.21]

3 Oxygen requirement at 28 to 30 days of age (all infants) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 3 Oxygen requirement at 28 to 30 days of age (all infants).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 3 Oxygen requirement at 28 to 30 days of age (all infants).

3.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.88, 1.12]

3.2 Treatment

3

1510

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.98, 1.21]

4 Oxygen requirement at 36 weeks postmenstrual age (all infants) Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age (all infants).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age (all infants).

4.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.79, 1.19]

4.2 Treatment

5

1564

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.11]

5 Death or oxygen requirement at 28 to 30 days of age Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 5 Death or oxygen requirement at 28 to 30 days of age.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 5 Death or oxygen requirement at 28 to 30 days of age.

5.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.93, 1.13]

5.2 Treatment

2

1401

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.96, 1.15]

6 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.6

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 6 Death or oxygen requirement at 36 weeks postmenstrual age.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 6 Death or oxygen requirement at 36 weeks postmenstrual age.

6.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.17]

6.2 Treatment

3

2009

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.86, 1.06]

7 Received > one dose of surfactant Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.7

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 7 Received > one dose of surfactant.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 7 Received > one dose of surfactant.

7.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.16]

7.2 Treatment

5

2178

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.93, 1.06]

8 Pneumothorax Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.8

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 8 Pneumothorax.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 8 Pneumothorax.

8.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.43, 1.36]

8.2 Treatment

6

2224

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.85, 1.51]

9 Air leak syndromes Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.9

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 9 Air leak syndromes.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 9 Air leak syndromes.

9.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.84, 1.60]

9.2 Treatment

3

2022

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.82, 1.28]

10 Pulmonary hemorrhage Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.10

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 10 Pulmonary hemorrhage.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 10 Pulmonary hemorrhage.

10.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.88, 2.39]

10.2 Treatment

4

2138

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.74, 1.59]

11 Treated patent ductus arteriosus (PDA) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.11

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 11 Treated patent ductus arteriosus (PDA).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 11 Treated patent ductus arteriosus (PDA).

11.1 Treatment

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.07, 1.34]

12 Culture‐confirmed bacterial sepsis Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.12

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 12 Culture‐confirmed bacterial sepsis.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 12 Culture‐confirmed bacterial sepsis.

12.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.91, 1.28]

12.2 Treatment

6

2228

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.87, 1.15]

13 Necrotizing enterocolitis (any stage) Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.13

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 13 Necrotizing enterocolitis (any stage).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 13 Necrotizing enterocolitis (any stage).

13.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.74, 1.42]

13.2 Treatment

5

2191

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.78, 1.33]

14 Periventricular leukomalacia Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.14

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 14 Periventricular leukomalacia.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 14 Periventricular leukomalacia.

14.1 Prevention

1

713

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.29, 1.26]

14.2 Treatment

1

1275

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.59, 1.73]

15 Retinopathy of prematurity in infants examined (all stages) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.15

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 15 Retinopathy of prematurity in infants examined (all stages).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 15 Retinopathy of prematurity in infants examined (all stages).

15.1 Prevention

2

1011

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.86, 1.12]

15.2 Treatment

3

1662

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.16]

16 Retinopathy of prematurity in infants examined (severe stage 3 or greater) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.16

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 16 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 16 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

16.1 Prevention

1

637

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.77, 1.69]

16.2 Treatment

1

1001

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.64, 1.33]

17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.17

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades).

17.1 Prevention

1

713

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.87, 1.24]

17.2 Treatment

3

1434

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.98, 1.33]

18 Severe IVH in infants receiving neuroimaging Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.18

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 18 Severe IVH in infants receiving neuroimaging.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 18 Severe IVH in infants receiving neuroimaging.

18.1 Prevention

2

1087

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.89, 1.83]

18.2 Treatment

5

2040

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.68, 1.09]

Open in table viewer
Comparison 2. Bovine lung lavage surfactant vs. porcine minced lung

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality prior to discharge Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.4 [0.51, 3.87]

Analysis 2.1

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 1 Mortality prior to discharge.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 1 Mortality prior to discharge.

2 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.19, 3.04]

Analysis 2.2

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 2 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 2 Oxygen requirement at 36 weeks postmenstrual age.

3 Air leak syndromes Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.68]

Analysis 2.3

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 3 Air leak syndromes.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 3 Air leak syndromes.

4 Necrotizing enterocolitis (any stage) Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.68]

Analysis 2.4

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 4 Necrotizing enterocolitis (any stage).

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 4 Necrotizing enterocolitis (any stage).

5 Retinopathy of prematurity in infants examined (all stages) Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.8 [0.24, 2.66]

Analysis 2.5

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 5 Retinopathy of prematurity in infants examined (all stages).

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 5 Retinopathy of prematurity in infants examined (all stages).

6 Severe IVH Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.29, 2.41]

Analysis 2.6

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 6 Severe IVH.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 6 Severe IVH.

Open in table viewer
Comparison 3. Modified bovine minced lung vs. porcine minced lung

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

2

320

Risk Ratio (M‐H, Fixed, 95% CI)

1.48 [0.72, 3.07]

Analysis 3.1

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 1 Neonatal mortality.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 1 Neonatal mortality.

2 Mortality prior to discharge Show forest plot

9

901

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [1.04, 2.00]

Analysis 3.2

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 2 Mortality prior to discharge.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 2 Mortality prior to discharge.

3 Oxygen requirement at 28 to 30 days of age Show forest plot

2

320

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.77, 1.23]

Analysis 3.3

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 3 Oxygen requirement at 28 to 30 days of age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 3 Oxygen requirement at 28 to 30 days of age.

4 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

9

899

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.79, 1.12]

Analysis 3.4

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

5 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

448

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [1.04, 1.64]

Analysis 3.5

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

6 Received > one dose of surfactant Show forest plot

6

786

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [1.29, 1.92]

Analysis 3.6

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 6 Received > one dose of surfactant.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 6 Received > one dose of surfactant.

7 Pneumothorax Show forest plot

6

669

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.71, 2.17]

Analysis 3.7

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 7 Pneumothorax.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 7 Pneumothorax.

8 Air leak syndromes Show forest plot

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.98, 6.68]

Analysis 3.8

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 8 Air leak syndromes.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 8 Air leak syndromes.

9 Pulmonary hemorrhage Show forest plot

8

871

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.81, 2.02]

Analysis 3.9

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 9 Pulmonary hemorrhage.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 9 Pulmonary hemorrhage.

10 Treated patent ductus arteriosus (PDA) Show forest plot

3

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.28, 2.70]

Analysis 3.10

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 10 Treated patent ductus arteriosus (PDA).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 10 Treated patent ductus arteriosus (PDA).

11 Culture‐confirmed bacterial sepsis Show forest plot

6

526

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.87, 1.46]

Analysis 3.11

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 11 Culture‐confirmed bacterial sepsis.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 11 Culture‐confirmed bacterial sepsis.

12 Necrotizing enterocolitis (any stage) Show forest plot

7

701

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.50, 1.33]

Analysis 3.12

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 12 Necrotizing enterocolitis (any stage).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 12 Necrotizing enterocolitis (any stage).

13 Periventricular leukomalacia Show forest plot

1

47

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.07, 15.72]

Analysis 3.13

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 13 Periventricular leukomalacia.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 13 Periventricular leukomalacia.

14 Retinopathy of prematurity in infants examined (all stages) Show forest plot

3

230

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.29, 1.26]

Analysis 3.14

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 14 Retinopathy of prematurity in infants examined (all stages).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 14 Retinopathy of prematurity in infants examined (all stages).

15 Retinopathy of prematurity in infants examined (severe stage 3 or greater) Show forest plot

4

222

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.09, 0.09]

Analysis 3.15

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 15 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 15 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

16 Intraventricular hemorrhage (all grades) Show forest plot

4

318

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.64, 1.50]

Analysis 3.16

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 16 Intraventricular hemorrhage (all grades).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 16 Intraventricular hemorrhage (all grades).

17 Severe IVH Show forest plot

7

705

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.83, 1.97]

Analysis 3.17

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 17 Severe IVH.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 17 Severe IVH.

Open in table viewer
Comparison 4. Modified bovine minced lung vs. porcine lung lavage

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality prior to discharge Show forest plot

1

44

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.60, 1.99]

Analysis 4.1

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 1 Mortality prior to discharge.

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 1 Mortality prior to discharge.

2 Pneumothorax Show forest plot

1

44

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.01, 0.73]

Analysis 4.2

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 2 Pneumothorax.

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 2 Pneumothorax.

Open in table viewer
Comparison 5. Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.1

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 1 Neonatal mortality.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 1 Neonatal mortality.

1.1 Initial dose ≤ 100 mg/kg porcine minced lung

2

221

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.55, 2.62]

1.2 Initial dose ˃ 100 mg/kg porcine minced lung

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

2.69 [0.74, 9.86]

2 Mortality prior to discharge Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.2

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 2 Mortality prior to discharge.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 2 Mortality prior to discharge.

2.1 Initial dose ≤ 100 mg/kg porcine minced lung

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.61, 1.96]

2.2 Initial dose ˃ 100 mg/kg porcine minced lung

7

736

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [1.11, 2.38]

3 Oxygen requirement at 28 to 30 days of age Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.3

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 3 Oxygen requirement at 28 to 30 days of age.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 3 Oxygen requirement at 28 to 30 days of age.

3.1 Initial dose ≤ 100 mg/kg porcine minced lung

2

221

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.25]

3.2 Initial dose ˃ 100 mg/kg porcine minced lung

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.76, 1.34]

4 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.4

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

4.1 Initial dose ≤ 100 mg/kg porcine minced lung

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.65, 1.37]

4.2 Initial dose ˃ 100 mg/kg porcine minced lung

6

608

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.84, 1.38]

5 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 5.5

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

5.1 Initial dose ≤ 100 mg/kg porcine minced lung

1

175

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.76, 1.43]

5.2 Initial dose ˃ 100 mg/kg porcine minced lung

3

363

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [1.08, 1.79]

Forest plot of comparison: 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, outcome: 1.2 Mortality prior to discharge.
Figuras y tablas -
Figure 1

Forest plot of comparison: 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, outcome: 1.2 Mortality prior to discharge.

Forest plot of comparison: 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, outcome: 1.4 Oxygen requirement at 36 weeks postmenstrual age (all infants).
Figuras y tablas -
Figure 2

Forest plot of comparison: 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, outcome: 1.4 Oxygen requirement at 36 weeks postmenstrual age (all infants).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 1 Neonatal mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 1 Neonatal mortality.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 2 Mortality prior to discharge.
Figuras y tablas -
Analysis 1.2

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 2 Mortality prior to discharge.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 3 Oxygen requirement at 28 to 30 days of age (all infants).
Figuras y tablas -
Analysis 1.3

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 3 Oxygen requirement at 28 to 30 days of age (all infants).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age (all infants).
Figuras y tablas -
Analysis 1.4

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age (all infants).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 5 Death or oxygen requirement at 28 to 30 days of age.
Figuras y tablas -
Analysis 1.5

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 5 Death or oxygen requirement at 28 to 30 days of age.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 6 Death or oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 1.6

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 6 Death or oxygen requirement at 36 weeks postmenstrual age.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 7 Received > one dose of surfactant.
Figuras y tablas -
Analysis 1.7

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 7 Received > one dose of surfactant.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 8 Pneumothorax.
Figuras y tablas -
Analysis 1.8

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 8 Pneumothorax.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 9 Air leak syndromes.
Figuras y tablas -
Analysis 1.9

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 9 Air leak syndromes.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 10 Pulmonary hemorrhage.
Figuras y tablas -
Analysis 1.10

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 10 Pulmonary hemorrhage.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 11 Treated patent ductus arteriosus (PDA).
Figuras y tablas -
Analysis 1.11

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 11 Treated patent ductus arteriosus (PDA).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 12 Culture‐confirmed bacterial sepsis.
Figuras y tablas -
Analysis 1.12

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 12 Culture‐confirmed bacterial sepsis.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 13 Necrotizing enterocolitis (any stage).
Figuras y tablas -
Analysis 1.13

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 13 Necrotizing enterocolitis (any stage).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 14 Periventricular leukomalacia.
Figuras y tablas -
Analysis 1.14

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 14 Periventricular leukomalacia.

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 15 Retinopathy of prematurity in infants examined (all stages).
Figuras y tablas -
Analysis 1.15

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 15 Retinopathy of prematurity in infants examined (all stages).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 16 Retinopathy of prematurity in infants examined (severe stage 3 or greater).
Figuras y tablas -
Analysis 1.16

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 16 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades).
Figuras y tablas -
Analysis 1.17

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades).

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 18 Severe IVH in infants receiving neuroimaging.
Figuras y tablas -
Analysis 1.18

Comparison 1 Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract, Outcome 18 Severe IVH in infants receiving neuroimaging.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 1 Mortality prior to discharge.
Figuras y tablas -
Analysis 2.1

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 1 Mortality prior to discharge.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 2 Oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 2.2

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 2 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 3 Air leak syndromes.
Figuras y tablas -
Analysis 2.3

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 3 Air leak syndromes.

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 4 Necrotizing enterocolitis (any stage).
Figuras y tablas -
Analysis 2.4

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 4 Necrotizing enterocolitis (any stage).

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 5 Retinopathy of prematurity in infants examined (all stages).
Figuras y tablas -
Analysis 2.5

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 5 Retinopathy of prematurity in infants examined (all stages).

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 6 Severe IVH.
Figuras y tablas -
Analysis 2.6

Comparison 2 Bovine lung lavage surfactant vs. porcine minced lung, Outcome 6 Severe IVH.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 1 Neonatal mortality.
Figuras y tablas -
Analysis 3.1

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 1 Neonatal mortality.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 2 Mortality prior to discharge.
Figuras y tablas -
Analysis 3.2

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 2 Mortality prior to discharge.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 3 Oxygen requirement at 28 to 30 days of age.
Figuras y tablas -
Analysis 3.3

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 3 Oxygen requirement at 28 to 30 days of age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 3.4

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 3.5

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 6 Received > one dose of surfactant.
Figuras y tablas -
Analysis 3.6

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 6 Received > one dose of surfactant.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 7 Pneumothorax.
Figuras y tablas -
Analysis 3.7

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 7 Pneumothorax.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 8 Air leak syndromes.
Figuras y tablas -
Analysis 3.8

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 8 Air leak syndromes.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 9 Pulmonary hemorrhage.
Figuras y tablas -
Analysis 3.9

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 9 Pulmonary hemorrhage.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 10 Treated patent ductus arteriosus (PDA).
Figuras y tablas -
Analysis 3.10

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 10 Treated patent ductus arteriosus (PDA).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 11 Culture‐confirmed bacterial sepsis.
Figuras y tablas -
Analysis 3.11

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 11 Culture‐confirmed bacterial sepsis.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 12 Necrotizing enterocolitis (any stage).
Figuras y tablas -
Analysis 3.12

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 12 Necrotizing enterocolitis (any stage).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 13 Periventricular leukomalacia.
Figuras y tablas -
Analysis 3.13

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 13 Periventricular leukomalacia.

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 14 Retinopathy of prematurity in infants examined (all stages).
Figuras y tablas -
Analysis 3.14

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 14 Retinopathy of prematurity in infants examined (all stages).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 15 Retinopathy of prematurity in infants examined (severe stage 3 or greater).
Figuras y tablas -
Analysis 3.15

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 15 Retinopathy of prematurity in infants examined (severe stage 3 or greater).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 16 Intraventricular hemorrhage (all grades).
Figuras y tablas -
Analysis 3.16

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 16 Intraventricular hemorrhage (all grades).

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 17 Severe IVH.
Figuras y tablas -
Analysis 3.17

Comparison 3 Modified bovine minced lung vs. porcine minced lung, Outcome 17 Severe IVH.

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 1 Mortality prior to discharge.
Figuras y tablas -
Analysis 4.1

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 1 Mortality prior to discharge.

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 2 Pneumothorax.
Figuras y tablas -
Analysis 4.2

Comparison 4 Modified bovine minced lung vs. porcine lung lavage, Outcome 2 Pneumothorax.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 1 Neonatal mortality.
Figuras y tablas -
Analysis 5.1

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 1 Neonatal mortality.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 2 Mortality prior to discharge.
Figuras y tablas -
Analysis 5.2

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 2 Mortality prior to discharge.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 3 Oxygen requirement at 28 to 30 days of age.
Figuras y tablas -
Analysis 5.3

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 3 Oxygen requirement at 28 to 30 days of age.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 5.4

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 4 Oxygen requirement at 36 weeks postmenstrual age.

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.
Figuras y tablas -
Analysis 5.5

Comparison 5 Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage), Outcome 5 Death or oxygen requirement at 36 weeks postmenstrual age.

Summary of findings for the main comparison. Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for prevention of RDS

Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for prevention of RDS (Comparision 1: Prevention studies)

Patient or population: Preterm infants for prevention of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Modified bovine minced lung surfactant extract

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with modified bovine minced lung surfactant extract

Risk with Bovine lung lavage surfactant extract

Mortality prior to discharge (from any cause)

107 per 1000

133 per 1000
(96 to 183)

RR 1.24
(0.90 to 1.71)

1123
(2 RCTs)

⨁⨁⨁◯
MODERATE 1

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm) and and the total number of events does not meet the optimal information size (OIS).

Oxygen requirement at 36 weeks' postmenstrual age

341 per 1000

331 per 1000
(270 to 406)

RR 0.97
(0.79 to 1.19)

749
(1 RCT)

⨁⨁⨁◯
MODERATE 2

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Death or oxygen requirement at 36 weeks' postmenstrual age

409 per 1000

418 per 1000
(364 to 479)

RR 1.02
(0.89 to 1.17)

1133
(2 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the no effect. The total number of events meets the OIS

Pneumothorax.

67 per 1000

51 per 1000
(29 to 91)

RR 0.76
(0.43 to 1.36)

749
(1 RCT)

⨁⨁⨁◯
MODERATE 2

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm)

Pulmonary hemorrhage

44 per 1000

63 per 1000
(39 to 105)

RR 1.44
(0.88 to 2.39)

1123
(2 RCTs)

⨁⨁◯◯
LOW 3

Downgraded two levels due to very serious imprecision: 1) the 95% CI includes both no effect and appreciable harm. 2) the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 3000)

Severe IVH in infants receiving neuroimaging

87 per 1000

112 per 1000
(78 to 160)

RR 1.28
(0.89 to 1.83)

1087
(2 RCTs)

⨁⨁◯◯
LOW 4

Downgraded two levels due to very serious imprecision: 1) 95% CI includes both no effect and appreciable harm.2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 2000).

Neurodevelopmental outcome at approximately two years’ corrected age

see comments

see comments

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 95% CI includes benefit, no effect and appreciable harm and the total number of events does not meet the optimal information size

2 95% CI includes benefit, no effect and appreciable harm

3 95% CI includes benefit, no effect and appreciable harm and the OIS to detect a clinically beneficial effect if there is one is > 3000

4 95% CI includes benefit, no effect and appreciable harm and the OIS to detect a clinically beneficial effect if there is one is > 2000

Figuras y tablas -
Summary of findings for the main comparison. Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for prevention of RDS
Summary of findings 2. Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for treatment of RDS

Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Modified bovine minced lung surfactant extract

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with modified bovine minced lung surfactant extract

Risk with Bovine lung lavage surfactant extract

Mortality prior to discharge

131 per 1000

128 per 1000
(103 to 158)

RR 0.98
(0.79 to 1.21)

2231
(6 RCTs)

⨁⨁⨁◯
MODERATE 1

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm) and the total number of events does not meet the OIS.

Oxygen requirement at 36 weeks' postmenstrual age (all infants)

312 per 1000

297 per 1000
(256 to 347)

RR 0.95
(0.82 to 1.11)

1564
(5 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the probability of no effect. Estimations are based in more than 300 events in each arm.

Death or oxygen requirement at 36 weeks' postmenstrual age

421 per 1000

400 per 1000
(362 to 446)

RR 0.95
(0.86 to 1.06)

2009
(3 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the probability of no effect. Estimations are based in more than 300 events in each arm.

Pneumothorax

73 per 1000

83 per 1000
(62 to 110)

RR 1.14
(0.85 to 1.51)

2224
(6 RCTs)

⨁⨁◯◯
LOW 1 2

Downgraded two levels due to:

1) Serious imprecision (95% CI includes both no effect and appreciable harm).

2) Inconsistency: Unexplained heterogeneity, with point estimates widely different; 95% CI not overlapping and leading to different conclusions (P value 0.03, Chi² 10.66, I² = 62%)

Pulmonary hemorrhage

44 per 1000

48 per 1000
(33 to 71)

RR 1.08
(0.74 to 1.59)

2138
(4 RCTs)

⨁⨁⨁◯
MODERATE 1

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm)

Severe IVH in infants receiving neuroimaging

125 per 1000

108 per 1000
(85 to 136)

RR 0.86
(0.68 to 1.09)

2040
(5 RCTs)

⨁⨁⨁◯
MODERATE 3

Downgraded one level due to imprecision (95% CI includes benefits, no effect and appreciable harm). The optimal information size to reliably detect a clinically beneficial effect if there is one is > 7000

Neurodevelopmental outcome at approximately two years’ corrected age

see comments

see comments

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 95% CI includes benefits, no effect and appreciable harm, and the total number of events does not meet the OIS

2 Unexplained heterogeneity, with point estimates widely different and CI not overlapping and leading to different conclusions (P value 0.03, Chi² 10.66, I² = 62%)

3 95% CI of the pooled effect crosses 1 and the optimal information size to reliably detect a clinically beneficial effect if there is one is > 7000

Figuras y tablas -
Summary of findings 2. Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for treatment of RDS
Summary of findings 3. Bovine lung lavage surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Bovine lung lavage surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Porcine minced lung surfactant extract

Outcomes

Anticipated absolute effects*

(95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with porcine minced lung surfactant extract

Risk with Bovine lung lavage surfactant extract

Mortality prior to discharge

185 per 1000

259 per 1000
(94 to 717)

RR 1.40
(0.51 to 3.87)

54
(1 RCT)

⨁⨁◯◯
LOW 1

Downgraded two levels due to very serious imprecision: 1) the 95% CI includes both no effect and appreciable harm.

2) the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Oxygen requirement at 36 weeks' postmenstrual age

148 per 1000

111 per 1000
(28 to 450)

RR 0.75
(0.19 to 3.04)

54
(1 RCT)

⨁⨁◯◯
LOW 1

Downgraded two levels due to:

1. Serious imprecision (95% CI includes both no effect and appreciable harm).

2. Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Death or oxygen requirement at 36 weeks' postmenstrual age

see comments

see comments

Not reported in any of the studies

Pneumothorax

see comments

see comments

Not reported in any of the studies

Pulmonary hemorrhage

see comments

see comments

Not reported in any of the studies

Severe intraventricular hemorrhage in infants who received neuroimaging

222 per 1000

184 per 1000
(64 to 536)

RR 0.83
(0.29 to 2.41)

54
(1 RCT)

⨁◯◯◯
VERY LOW 2 3

Downgraded three levels due to:

1. potential risk of bias (lack of blinding of outcome assessment)

2. very serious imprecision: (95% CI includes both no effect and appreciable harm) and the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Neurodevelopmental outcome at approximately two years’ corrected age

see comments

see comments

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 95% CI of the pooled effect crosses 1 and the optimal information size to detect a clinically beneficial effect if there is one is > 1000

2 We downgraded because lack of blinding of patients, providers and blinding of outcome assessment

3 95% CI of the pooled effect crosses 1 and the optimal information size to detect a clinically beneficial effect if there is one is > 1000

Figuras y tablas -
Summary of findings 3. Bovine lung lavage surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS
Summary of findings 4. Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Modified bovine minced lung surfactant extract
Comparison: Porcine minced lung surfactant extract

Outcomes

Anticipated absolute effects*

(95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with porcine minced lung surfactant extract

Risk with Modified bovine minced lung surfactant extract

Mortality prior to hospital discharge (from any cause)

113 per 1000

162 per 1000
(117 to 225)

RR 1.44
(1.04 to 2.00)

901
(9 RCTs)

⨁⨁⨁◯
MODERATE 1

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Despite the high risk of bias4 we did not downgrade the quality because of its lower impact on this outcome.

Oxygen requirement at 36 weeks' postmenstrual age

282 per 1000

293 per 1000
(234 to 370)

RR 1.04 (0.83 to 1.31)

773
(8RCTs)

⨁⨁⨁◯
MODERATE 2

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Despite the high risk of bias4 we did not downgrade the quality because of its lower impact on this outcome.

Death or oxygen requirement at 36 weeks' postmenstrual age

380 per 1000

494 per 1000
(395 to 623)

RR 1.30
(1.04 to 1.64)

448
(3 RCTs)

⨁⨁⨁◯
MODERATE 1

Downgraded one level due to imprecision (total number of events does not meet the OIS)

Pneumothorax

63 per 1000

78 per 1000
(45 to 137)

RR 1.24
(0.71 to 2.17)

669
(6 RCTs)

⨁⨁◯◯
LOW 3

Downgraded two levels due to very serious imprecision:

1) the 95% CI includes both no effect and appreciable harm.

2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 5000)

Pulmonary hemorrhage

72 per 1000

92 per 1000
(58 to 146)

RR 1.28
(0.81 to 2.02)

871
(8 RCTs)

⨁⨁◯◯
LOW 3

Downgraded two levels due to very serious imprecision:

1) the 95% CI includes both no effect and appreciable harm.

2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 5000)

Severe intraventricular hemorrhage in infants who received neuroimaging

97 per 1000

124 per 1000
(80 to 190)

RR 1.28
(0.83 to 1.97)

705
(7 RCTs)

⨁◯◯◯
VERY LOW 4 5

Downgraded three levels due to:

1. Potential risk of bias and 2. serious imprecision: 1) the 95% CI includes both no effect and appreciable harm; and 2) Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 3000)

Neurodevelopmental outcome at approximately two years’ corrected age

see comments

see comments

Not reported in any studies

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 The total number of events does not meet the OIS

2 95% CI includes benefit, no effect and appreciable harm. Total number of events does not meet the optimal information size.

3 95% CI of the pooled effect crosses 1 and the optimal information size to detect a clinically beneficial effect if there is one is > 5000

4 Studies that carried large weight for the overall effect estimate are classified as high or unclear risk of bias due to lack of blinding in patients, and outcome assessment

5 95% CI of the pooled effect widely crosses 1 and the optimal information size to detect a clinically beneficial effect if there is one is > 3000

Figuras y tablas -
Summary of findings 4. Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS
Summary of findings 5. Modified bovine minced lung surfactant extract compared with porcine lung lavage surfactant in preterm infants for treatment of RDS

Modified bovine minced lung surfactant extract compared with porcine lung lavage surfactant in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Modified bovine minced lung surfactant extract
Comparison: Porcine lung lavage surfactant

Outcomes

Anticipated absolute effects*

(95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with porcine lung lavage surfactant

Risk with Modified bovine minced lung surfactant extract

Mortality prior to hospital discharge (from any cause)

476 per 1000

524 per 1000
(286 to 948)

RR 1.10
(0.60 to 1.99)

44
(1 RCT)

⨁⨁◯◯
LOW 1

Downgraded two levels due to serious imprecision:

1) The 95% CI includes both no effect and appreciable harm.

2) Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 700).

Oxygen requirement at 36 weeks' postmenstrual age

see comments

see comments

Not reported in any of the studies

Death or oxygen requirement at 36 weeks' postmenstrual age

see comments

see comments

Not reported in any of the studies

Pneumothorax

429 per 1000

43 per 1000
(4 to 313)

RR 0.10
(0.01 to 0.73)

44
(1 RCT)

⨁⨁⨁⨁
HIGH

Pulmonary hemorrhage

see comments

see comments

Not reported in any of the studies

Severe intraventricular hemorrhage in infants who received neuroimaging

see comments

see comments

Not reported in any of the studies

Neurodevelopmental outcome at approximately two years corrected age

see comments

see comments

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 95 % CI of the pooled effect crosses 1 and the optimal information size to detect a clinically beneficial effect if there is one is > 700

Figuras y tablas -
Summary of findings 5. Modified bovine minced lung surfactant extract compared with porcine lung lavage surfactant in preterm infants for treatment of RDS
Comparison 1. Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.79, 1.80]

1.2 Treatment

3

1451

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.65, 1.26]

2 Mortality prior to discharge Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.90, 1.71]

2.2 Treatment

6

2231

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.79, 1.21]

3 Oxygen requirement at 28 to 30 days of age (all infants) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.88, 1.12]

3.2 Treatment

3

1510

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.98, 1.21]

4 Oxygen requirement at 36 weeks postmenstrual age (all infants) Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.79, 1.19]

4.2 Treatment

5

1564

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.82, 1.11]

5 Death or oxygen requirement at 28 to 30 days of age Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.93, 1.13]

5.2 Treatment

2

1401

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.96, 1.15]

6 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.17]

6.2 Treatment

3

2009

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.86, 1.06]

7 Received > one dose of surfactant Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.16]

7.2 Treatment

5

2178

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.93, 1.06]

8 Pneumothorax Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Prevention

1

749

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.43, 1.36]

8.2 Treatment

6

2224

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.85, 1.51]

9 Air leak syndromes Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.84, 1.60]

9.2 Treatment

3

2022

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.82, 1.28]

10 Pulmonary hemorrhage Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.88, 2.39]

10.2 Treatment

4

2138

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.74, 1.59]

11 Treated patent ductus arteriosus (PDA) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 Treatment

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.07, 1.34]

12 Culture‐confirmed bacterial sepsis Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.91, 1.28]

12.2 Treatment

6

2228

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.87, 1.15]

13 Necrotizing enterocolitis (any stage) Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Prevention

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.74, 1.42]

13.2 Treatment

5

2191

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.78, 1.33]

14 Periventricular leukomalacia Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 Prevention

1

713

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.29, 1.26]

14.2 Treatment

1

1275

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.59, 1.73]

15 Retinopathy of prematurity in infants examined (all stages) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 Prevention

2

1011

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.86, 1.12]

15.2 Treatment

3

1662

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.89, 1.16]

16 Retinopathy of prematurity in infants examined (severe stage 3 or greater) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

16.1 Prevention

1

637

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.77, 1.69]

16.2 Treatment

1

1001

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.64, 1.33]

17 Intraventricular hemorrhage in infants receiving neuroimaging (all grades) Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

17.1 Prevention

1

713

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.87, 1.24]

17.2 Treatment

3

1434

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.98, 1.33]

18 Severe IVH in infants receiving neuroimaging Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1 Prevention

2

1087

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.89, 1.83]

18.2 Treatment

5

2040

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.68, 1.09]

Figuras y tablas -
Comparison 1. Bovine lung lavage surfactant extract vs. modified bovine minced lung surfactant extract
Comparison 2. Bovine lung lavage surfactant vs. porcine minced lung

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality prior to discharge Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.4 [0.51, 3.87]

2 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.19, 3.04]

3 Air leak syndromes Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.68]

4 Necrotizing enterocolitis (any stage) Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.68]

5 Retinopathy of prematurity in infants examined (all stages) Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.8 [0.24, 2.66]

6 Severe IVH Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.29, 2.41]

Figuras y tablas -
Comparison 2. Bovine lung lavage surfactant vs. porcine minced lung
Comparison 3. Modified bovine minced lung vs. porcine minced lung

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

2

320

Risk Ratio (M‐H, Fixed, 95% CI)

1.48 [0.72, 3.07]

2 Mortality prior to discharge Show forest plot

9

901

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [1.04, 2.00]

3 Oxygen requirement at 28 to 30 days of age Show forest plot

2

320

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.77, 1.23]

4 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

9

899

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.79, 1.12]

5 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

448

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [1.04, 1.64]

6 Received > one dose of surfactant Show forest plot

6

786

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [1.29, 1.92]

7 Pneumothorax Show forest plot

6

669

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.71, 2.17]

8 Air leak syndromes Show forest plot

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.98, 6.68]

9 Pulmonary hemorrhage Show forest plot

8

871

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.81, 2.02]

10 Treated patent ductus arteriosus (PDA) Show forest plot

3

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.28, 2.70]

11 Culture‐confirmed bacterial sepsis Show forest plot

6

526

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.87, 1.46]

12 Necrotizing enterocolitis (any stage) Show forest plot

7

701

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.50, 1.33]

13 Periventricular leukomalacia Show forest plot

1

47

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.07, 15.72]

14 Retinopathy of prematurity in infants examined (all stages) Show forest plot

3

230

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.29, 1.26]

15 Retinopathy of prematurity in infants examined (severe stage 3 or greater) Show forest plot

4

222

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.09, 0.09]

16 Intraventricular hemorrhage (all grades) Show forest plot

4

318

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.64, 1.50]

17 Severe IVH Show forest plot

7

705

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.83, 1.97]

Figuras y tablas -
Comparison 3. Modified bovine minced lung vs. porcine minced lung
Comparison 4. Modified bovine minced lung vs. porcine lung lavage

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality prior to discharge Show forest plot

1

44

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.60, 1.99]

2 Pneumothorax Show forest plot

1

44

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.01, 0.73]

Figuras y tablas -
Comparison 4. Modified bovine minced lung vs. porcine lung lavage
Comparison 5. Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Initial dose ≤ 100 mg/kg porcine minced lung

2

221

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.55, 2.62]

1.2 Initial dose ˃ 100 mg/kg porcine minced lung

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

2.69 [0.74, 9.86]

2 Mortality prior to discharge Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Initial dose ≤ 100 mg/kg porcine minced lung

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.61, 1.96]

2.2 Initial dose ˃ 100 mg/kg porcine minced lung

7

736

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [1.11, 2.38]

3 Oxygen requirement at 28 to 30 days of age Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Initial dose ≤ 100 mg/kg porcine minced lung

2

221

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.73, 1.25]

3.2 Initial dose ˃ 100 mg/kg porcine minced lung

1

197

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.76, 1.34]

4 Oxygen requirement at 36 weeks postmenstrual age Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Initial dose ≤ 100 mg/kg porcine minced lung

3

255

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.65, 1.37]

4.2 Initial dose ˃ 100 mg/kg porcine minced lung

6

608

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.84, 1.38]

5 Death or oxygen requirement at 36 weeks postmenstrual age Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Initial dose ≤ 100 mg/kg porcine minced lung

1

175

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.76, 1.43]

5.2 Initial dose ˃ 100 mg/kg porcine minced lung

3

363

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [1.08, 1.79]

Figuras y tablas -
Comparison 5. Modified bovine minced lung vs. porcine minced lung (based on initial surfactant dosage)